Drugs that target KIT and PDGFRa have transformed the way we treat GIST.  While these drugs may be very effective initially, most patients eventually become resistant to them. They develop additional or ‘secondary’ mutations in an area known as the ‘activation loop,’ which keep the tumor in a persistently activated state. Once this happens, drugs like Gleevec, Sutent, and Stivarga cannot gain access to the binding pocket in sufficient quantity to effectively control tumor growth.
Two new drugs, BLU-285 and DCC-2618, are under development to specifically target GIST’s harboring activation loop mutations.  Both drugs have demonstrated pre-clinical activity against primary and secondary mutations, including and most importantly, the PDGFRa D842V mutation.  Both BLU-285 and DCC-2618 have been moved from the dose-escalation phase to the dose expansion phase of study. A presentation of these findings was given by Dr. Michael Heinrich at the 2017 GISTS Summit and recent trial data can be viewed here.
BLU-285 novel, oral, investigational drug focusing on inhibition of PDGFRα D842V and KIT Exon 17 mutants.  The shape of the BLU-285 molecule is designed to better enable binding to the ATP pocket.  A phase III trial comparing BLU-285 against Regorafenib as a third line of defense is planned.  A press release by Blueprint Pharmaceuticals can be found here.  
DCC-2618:  Is a novel, oral, investigational potent pan-KIT and PDGFRα kinase inhibitor with activity across a broad range of tyrosine kinase inhibitor mutations. These include primary KIT exon’s 9,11, or 17 as well as secondary KIT mutations across exon’s 13, 14, 17, and 18.  The shape of the DCC-2618 molecule is designed to restore accessibility to the binding pocket when it is blocked by the presence of a loop activation mutation.  A Phase III trial for DCC-2618 as the fourth line of treatment for GIST is planned.  An article about DCC-2618 in the European Society for Clinical Oncology journal can be viewed here.  You can also  view the clinical trial protocol by clicking here.